The likelihood for a surgical cure of newly-diagnosed primary non-small cell lung cancers is strongly dependent upon the local extent of the cancer, particularly whether or not the mediastinal lymph nodes are involved with cancer. Five year survivals of approximately 8% ar seen in patients whose mediastinal lymph nodes are involved with cancer vs. 46% when there are no mediastinal metastases. The potentially curative surgical procedures of thoracotomy with lobectomy or pneumonectomy cause substantial mortality (+5%) and morbidity (+10%) and are inappropriate of the patients disease burden is so extensive as to be non-resectable and non-curable. While standard cross-sectional imaging methods such as CT or MRI are routinely used pre-operatively for staging, recent studies have demonstrated that these methods are: 1) incapable of detecting small foci of metastatic cancer in mediastinal lymph nodes that are not enlarged, and 20 incapable of specifically determining whether borderline or moderately-enlarged mediastinal lymph nodes are involved with cancer. Thus, the sensitivity and specificity of these cross-sectional methods are not optimal. We propose to prospectively evaluate the accuracy of pre-operative PET scanning using FDG and 11C-L- methionine for the detection of mediastinal tumor metastases in patients with newly- diagnosed non-small cell lung cancers. CT and PET scans performed on such patients prior to surgery will first be interpreted separately, then the CT and PET scans will be interpreted together. In addition, the CT and PET images will be co-registered using computer image fusion methods and a series of anatomic/metabolic fusion images produced. These metabolic/anatomic fusion images will also be interpreted to enhance the anatomic localization and diagnostic accuracy of the PET staging procedure. Patients will also receive an i.v. tracer injection of FDG immediately prior to surgery, so that the uptake of FDG can be measured in biopsy specimens containing tumor-involved and normal tissues. Thoracic surgery, specifically sampling well-defined American Thoracic Society designated mediastinal nodal regions, will be performed. Nodal histology and FDG uptake in the resected cancers and lymph nodes will be determined and correlated with the presence or absence of cancer. The accuracy of CT and PET interpreted independently, and then together both with, and without, the metabolic/anatomic fusion images, will then be compared to pathological 'truth'. These results will then be used to develop and optimize interpretative criteria for PET in the staging of the mediastinum in patients with non-small cell lung cancer. These criteria will be applied prospectively to patients imaged in the third and fourth year of the proposal. Through this study we expect to determine the accuracy, and thus the potential diagnostic utility, of FDG and 11C-L-methionine PET scanning in the pre-operative staging of patients with non-small cell lung cancers.